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Influence of 23 coronary artery disease variants on recurrent myocardial infarction or cardiac death: the GRACE Genetics Study.
- Source :
-
European heart journal [Eur Heart J] 2013 Apr; Vol. 34 (13), pp. 993-1001. Date of Electronic Publication: 2012 Nov 15. - Publication Year :
- 2013
-
Abstract
- Aims: A pooled analysis of 14 genome-wide association studies revealed 23 susceptibility loci for coronary artery disease (CAD), thereby providing the most comprehensive genetic blueprint of CAD susceptibility. Here, we evaluated whether these 23 loci also predispose to recurrent myocardial infarction (MI) or cardiac death following an acute coronary syndrome (ACS).<br />Methods and Results: A total of 2099 ACS patients enrolled in the Global Registry of Acute Coronary Events (GRACE) UK-Belgian study were prospectively followed for a median of 5 years (1668 days). C-allele carriers of the rs579459 variant, which is located upstream of the ABO gene and correlates with blood group A, were independently associated with recurrent MI [multivariable-adjusted hazard ratio (HR) 2.25, CI = 1.37-3.71; P = 0.001] and with recurrent MI or cardiac death [multivariable-adjusted (HR) 1.80, CI = 1.09-2.95; P = 0.021] within 5 years after an index ACS. The association of rs579459 was replicated in 1250 Polish patients with 6 months follow-up after an index ACS [multivariable-adjusted (HR) 2.70, CI = 1.26-5.82; P = 0.011 for recurrent MI]. Addition of rs579459 to a prediction model of 17 clinical risk factors improved risk classification for recurrent MI or cardiac death at 6 months as calculated by the integrated discrimination improvement method (P = 0.037), but not by C-statistics (P = 0.096).<br />Conclusion: In this observational study, rs579459 was independently associated with adverse cardiac outcome after ACS. A weak improvement in clinical risk prediction was also observed, suggesting that rs579459 should be further tested as a potentially relevant contributor to risk prediction models for adverse outcome following ACS.
- Subjects :
- ABO Blood-Group System genetics
Aged
Belgium epidemiology
Coronary Artery Disease mortality
Death, Sudden, Cardiac epidemiology
Female
Gene Frequency
Genetic Loci genetics
Genome-Wide Association Study
Genotype
Humans
Male
Middle Aged
Myocardial Infarction mortality
Phenotype
Poland epidemiology
Prognosis
Prospective Studies
Recurrence
Registries
Risk Factors
United Kingdom epidemiology
Coronary Artery Disease genetics
Death, Sudden, Cardiac etiology
Genetic Predisposition to Disease genetics
Myocardial Infarction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1522-9645
- Volume :
- 34
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- European heart journal
- Publication Type :
- Academic Journal
- Accession number :
- 23161703
- Full Text :
- https://doi.org/10.1093/eurheartj/ehs389